15-100885414-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000693.4(ALDH1A3):c.204+43G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0243 in 1,410,246 control chromosomes in the GnomAD database, including 605 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.030 (119 hom., cov: 32)
  • Exomes 𝑓: 0.024 (486 hom.)
• Consequence: ALDH1A3 NM_000693.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.566

Genes affected

ALDH1A3 (HGNC:409): (aldehyde dehydrogenase 1 family member A3) This gene encodes an aldehyde dehydrogenase enzyme that uses retinal as a substrate. Mutations in this gene have been associated with microphthalmia, isolated 8, and expression changes have also been detected in tumor cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 15-100885414-G-T is Benign according to our data. Variant chr15-100885414-G-T is described in ClinVar as [Benign]. Clinvar id is 1286007.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH1A3	NM_000693.4	c.204+43G>T		intron_variant		ENST00000329841.10
ALDH1A3	NM_001293815.2	c.204+43G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH1A3	ENST00000329841.10	c.204+43G>T		intron_variant		1	NM_000693.4	P1

Frequencies

GnomAD3 genomes AF: 0.0294 AC: 4481 AN: 152168 Hom.: 114 Cov.: 32

Gnomad AFR AF: 0.0518

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0197

Gnomad ASJ AF: 0.0576

Gnomad EAS AF: 0.0348

Gnomad SAS AF: 0.0474

Gnomad FIN AF: 0.00349

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0193

Gnomad OTH AF: 0.0320

GnomAD3 exomes AF: 0.0250 AC: 6030 AN: 241682 Hom.: 106 AF XY: 0.0253 AC XY: 3324 AN XY: 131160

Gnomad AFR exome AF: 0.0546

Gnomad AMR exome AF: 0.0130

Gnomad ASJ exome AF: 0.0596

Gnomad EAS exome AF: 0.0302

Gnomad SAS exome AF: 0.0428

Gnomad FIN exome AF: 0.00369

Gnomad NFE exome AF: 0.0196

Gnomad OTH exome AF: 0.0228

GnomAD4 exome AF: 0.0237 AC: 29808 AN: 1257960 Hom.: 486 Cov.: 17 AF XY: 0.0243 AC XY: 15486 AN XY: 636208

Gnomad4 AFR exome AF: 0.0544

Gnomad4 AMR exome AF: 0.0135

Gnomad4 ASJ exome AF: 0.0559

Gnomad4 EAS exome AF: 0.0419

Gnomad4 SAS exome AF: 0.0433

Gnomad4 FIN exome AF: 0.00439

Gnomad4 NFE exome AF: 0.0206

Gnomad4 OTH exome AF: 0.0275

GnomAD4 genome AF: 0.0296 AC: 4503 AN: 152286 Hom.: 119 Cov.: 32 AF XY: 0.0289 AC XY: 2154 AN XY: 74458

Gnomad4 AFR AF: 0.0522

Gnomad4 AMR AF: 0.0196

Gnomad4 ASJ AF: 0.0576

Gnomad4 EAS AF: 0.0348

Gnomad4 SAS AF: 0.0470

Gnomad4 FIN AF: 0.00349

Gnomad4 NFE AF: 0.0193

Gnomad4 OTH AF: 0.0317

Alfa AF: 0.0231 Hom.: 77

Bravo AF: 0.0314

Asia WGS AF: 0.0320 AC: 111 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 06, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	14
Dann	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4646655; hg19: chr15-101425619;